April 10, 2017

Chemical characterization of Extractables and Leachables (E&L) with the corresponding toxicological risk assessment are already mandated by regulatory agencies to ensure patient safety and successful submissions for medical devices. FDA regulations, USP and various ISO Standards namely 10993 part 18: Chemical Characterization of Materials, provide guidance to perform characterization of E&L.

Extractables are compounds that are released from a device or material into an extracting medium under exaggerated conditions of solvent, temperature and time. Leachables are compounds released from a device under conditions simulating clinical use and may be part of the “dose” of agents after a device is deployed as either a temporary or permanent implant.  These chemicals may originate from a variety of sources such as device components, packaging materials, process equipment, manufacturing, transport and storage, cleaning process, handling, etc.

The main challenge in Chemical Characterization is preparation of sample extracts and their analysis. The preparation depends on sample size, form, shape, composition and end use of the test article as defined in ISO 10993-part 12: Sample preparation and reference materials. This process requires a Quality by Design (QbD) strategy for targeted potential leachables depending on device complexity, composition, chemical and physical properties. Most often, the information is obtained from various sources: certificate of analysis, description of constituent materials, product labeling, stability, storage information, literature search, etc. This information provides a rationale for design of the exhaustive and simulated extraction plans.  Other challenges are identification and quantification of the unknown chemicals in addition to the tedious process of performing exhaustive extraction following routinely used techniques such as: Soxhlet, reflux, sonication, incubation, etc.

American Preclinical Services (APS) has acquired the latest, state-of-the art instrumentation and analytical expertise to perform Extractable and Leachable characterization on a variety of complex medical devices. In addition to instrumentation commonly used for separation, detection and identification of extracted components such as High Resolution Liquid Chromatography (HRLCMS), Gas Chromatography (GCMS), Inductively Coupled Plasma Mass Spectrometry, Fourier Transform Infrared Red, APS has recognized the value of the Accelerator Solvent Extractor (ASE) for the speed of extraction as well as its suitability for extraction of small devices and its ability to reduce the number of devices required for extractions.

In summary, American Preclinical Services is well positioned to assist clients with a Quality by Design (QbD) plan for E&L, to ensure a targeted investigation of extracts and leachates, to justify the results submitted for toxicological health risk assessment as required by ISO 10993 part 17: Establishment of allowable limits for leachables substances; and finally to aid in preparation of the final product submission to regulatory bodies.

Ask us how we can help, especially if the device size is small or device quantities are limited.